Substance originating in germinating seeds of gramineous plant and containing proteins and insoluble dietary fibers and use thereof

ABSTRACT

There is provided a substance which was isolated from the germinated seed of a grass family plant and which contains proteins and insoluble dietary fibers. There are also provided a pharmaceutical composition comprising as an active ingredient said substance which was isolated from the germinated seed of a grass family plant and which contains proteins and insoluble dietary fibers, and a food composition comprising said substance which was isolated from the germinated seed of a grass family plant and which contains proteins and insoluble dietary fibers, as well as uses of said substance.

TECHNICAL FIELD

The present invention relates to substances which are isolated from thegerminated seed of a grass family plant and which contain proteins andinsoluble dietary fibers, and uses thereof.

BACKGROUND ART

Ulcerative colitis has been rapidly growing in the number of patients inJapan since the 1970's. Main complaints of the disease include bloodydiarrhea, abdominal pains and the like. It is a chronic and diffusedisease of the large intestine, and, after the initial onset at therectum, it expands in an ascending manner to the deep part of the largeintestine with repeated remissions and flare-ups. The etiology of thedisease is unknown at present although its association with the diet hasbeen studied because the incidence of the disease increased with theWesternization of eating habits of the Japanese people. Some researcherssuggest that disease may be an autoimmune one, but no proposals on theetiology have obtained public acceptance so far. Very few drugs knowntoday are effective for the treatment of the disease except that asalazosulfapyridine is considered to have a therapeutic effect on mildcases of the disease. However, this drug is an antibiotic which isadministered in large quantities and thereby may cause problematic sideeffects such as diarrhea.

Even a possible therapeutic drug for ulcerative colitis currently underdevelopment is a mere improvement of the salazosulfapyridine, and theproblem of its side effects has not been completely solved.

Incidentally, cancer ranks top as a cause of deaths in Japan today. Itis an extremely intractable disease and the ratio of its successfultreatment is not very high at present. Current treatments of cancerinclude surgical removal, radiation exposure, chemotherapy(administration of anti-cancer agents), immunological therapy, etc.,with great strides being made in each method. However, cancer treatmentby a single method is believed to be a very difficult challenge.

The surgical process is a very effective means since it removes thetumor cells themselves but its sole use cannot attain a complete cureand, hence, radiation therapy and chemotherapy are simultaneouslyapplied in most cases. The biggest problem encountered in this case isthe side effects resulting from the radiation therapy and thechemotherapy. Either therapy attacks cancerous cells having highproliferating activities, so naturally severe damages are also inflictedupon tissues having high rate of growth such as mucosal epithelialcells. As a result, the intestinal mucosa is greatly damaged therebycausing a significant reduction in the absorption of orally administerednutrients and an ensuing severe diarrhea, which ultimately put thepatient in a greatly damaged condition. In an extreme case, the patientmay eventually die. However, very few effective means have so far beenavailable that can protect the damage of intestinal mucosa and preventdiarrhea.

If the bowels of patients suffering from colon cancer, Crohn's disease,etc., are extensively excised, post-operative dyspepsia and insufficientabsorption of electrolytes may cause the patients to have difficulty innormal bowel movement resulting in an extremely high incidence ofdiarrhea etc., and this can badly affect the patients in leading theirnormal social life. The same problem is shared by patients who wereforced to have an artificial anus for some reason. As a means to solvethese problems, there may be mentioned an oral liquid diet that leavesvery little residue after absorption. However, the oral liquid dietcauses many problems on the part of patients, such as economic burdens,some pains encountered in uptake, and mental burdens due to regulateddiets. Thus, there has been a great demand for an effective means thatcan alleviate these burdens.

Thus, it is an object of the present invention to provide safe materialsthat can solve the problems stated above.

It is another object of the present invention to provide pharmaceuticalcompositions and food compositions comprising said material.

It is a further object of the present invention to provide a method oftreating ulcerative colitis.

It is a still further object of the present invention to provide amethod of preventing or reducing the side effects of cancer treatments.

It is yet another object of the present invention to provide a method ofimproving the bowel movement of patients who have undergone intestinalablation or patients with an artificial anus.

DISCLOSURE OF THE INVENTION

After the intensive research conducted to solve the above-mentionedproblems, the inventors have discovered that a substance which wasseparated from the germinated seed of a grass family plant and whichcontains proteins and insoluble dietary fibers (hereinafter referred toas “the substance containing protein and insoluble dietary fibers”) canattain the above objects and thereby have completed the presentinvention. The gist of the present invention is as follows:

(1) a substance which was isolated from the germinated seed of a grassfamily plant and which contains proteins and insoluble dietary fibers;

(2) a pharmaceutical composition comprising as an active ingredient asubstance which was isolated from the germinated seed of a grass familyplant and which contains proteins and insoluble dietary fibers;

(3) a food composition comprising a substance which was isolated fromthe germinated seed of a grass family plant and which contains proteinsand insoluble dietary fibers;

(4) a method of treating ulcerative colitis comprising administering toa patient with ulcerative colitis an effective amount of a substancewhich was isolated from the germinated seed of a grass family plant andwhich contains proteins and insoluble dietary fibers;

(5) a method of preventing or reducing the side effects of cancertreatments comprising administering to a patient with a cancer aneffective amount of a substance which was isolated from the germinatedseed of a grass family plant and which contains proteins and insolubledietary fibers;

(6) a method of improving the bowel movement of a patient who hasundergone intestinal ablation comprising allowing the patient to take aneffective amount of a substance which was isolated from the germinatedseed of a grass family plant and which contains proteins and insolubledietary fibers;

(7) a method of improving the bowel movement of a patient with anartificial anus comprising allowing the patient to take an effectiveamount of a substance which was isolated from the germinated seed of agrass family plant and which contains proteins and insoluble dietaryfibers;

(8) use as a pharmaceutical drug of a substance which was isolated fromthe germinated seed of a grass family plant and which contains proteinsand insoluble dietary fibers;

(9) use, for the treatment of ulcerative colitis, of a substance whichwas isolated from the germinated seed of a grass family plant and whichcontains proteins and insoluble dietary fibers;

(10) use, for preventing or reducing the side effects of cancertreatments, of a substance which was isolated from the germinated seedof a grass family plant and which contains proteins and insolubledietary fibers;

(11) use as food of a substance which was isolated from the germinatedseed of a grass family plant and which contains proteins and insolubledietary fibers;

(12) use, for improving the bowel movement of a patient who hasundergone intestinal ablation, of a substance which was isolated fromthe germinated seed of a grass family plant and which contains proteinsand insoluble dietary fibers; and

(13) use, for improving the bowel movement of a patient with anartificial anus, of a substance which was isolated from the germinatedseed of a grass family plant and which contains proteins and insolubledietary fibers.

BRIEF EXPLANATION OF THE DRAWINGS

FIG. 1 shows the diarrhea scores of Experiment Group 1 and ComparativeGroup 1.

FIG. 2 is a pair of photographs showing the biological morphology of theappearance of stools from Comparative Group 1 (2-1) and Experiment Group1 (2-1).

FIG. 3 is a pair of photographs showing the biological morphology of theappearance of the colon mucosas of Comparative Group 1 and ExperimentGroup 1.

FIG. 4 shows the diarrhea scores of Experiment Groups 2 and 3 andComparative Group 2.

FIG. 5 shows the diarrhea scores of Experiment Group 4 and ComparativeGroup 3.

FIG. 6 shows the diarrhea scores of Experiment Group 5 and ComparativeGroup 4.

FIG. 7 shows the diarrhea scores of Experiment Groups 6 and 7 andComparative Groups 5 through 7.

FIG. 8 shows the dry weights of stools from Experiment Group 1a andComparative Groups 1a and 2a.

FIG. 9 is a set of photographs showing the biological morphology of theappearance of mucosas of the small intestines of Experiment Groups 1aand Comparative Groups 1a and 2a (9-2, 9-1, and 9-3, respectively).

FIG. 10 is a pair of photographs showing the appearance of stools fromExperiment Group 1b and Comparative Group 1b.

FIG. 11 is a pair of photographs showing the peripheral appearance ofthe anuses of Experiment Group 1b and Comparative Group 1b.

BEST MODE FOR CARRYING OUT THE INVENTION

As already mentioned, the substance containing proteins and insolubledietary fibers as used herein is a component obtained from thegerminated seed of a grass family plant. Grass family plants refer toall the plants that are classified into the grass family. Specifically,they include, but are not limited to, rice, barley, wheat, rye, millet,barnyard grass, corn, and the like. Among them, rice, barley, and ryeare preferred. The germinated seed of a grass family plant may be usedas a raw material in separating a substance containing proteins andinsoluble dietary fibers with the protein content being 10 to 70% byweight and the insoluble dietary fiber content 20 to 70% by weight, andpreferably with the protein content being 10 to 60% by weight and theinsoluble dietary fiber content 20 to 50% by weight. To determine theprotein content as used herein, then multiplied the nitrogen content isfirst obtained using the Kjeldahl method and by 6.25 which is a proteinconversion coefficient. The content of dietary fibers is the sum of theamounts of all dietary fibers present that are determined based on themethod shown in “Dietary Fiber”, Innami and Kiriyama, eds., pp. 38-40,1989, Daiichi Shuppan.

Specific methods for producing such the substance containing proteinsand insoluble dietary fibers include the following. i.e, the husks ofgerminated seeds of a grass family are gradually scraped off (until theweight becomes about 90% that of the original raw material), and thenthe fractions containing the aleurone layer and the germ are graduallyscraped off until the residue is endosperm only (until the weightbecomes about 80% that of the original raw material), and the aleuronelayer-germ fraction is obtained. The weights mentioned above are justguide figures and the fractionation is preferably carried out with thealeurone layer etc. are examined under an electron microscope.

Economically, it is preferred to use brewer's grains, which are thebarley malt remaining after use as the raw material of beer. As aspecific example of the method for obtaining the substance containingproteins and insoluble dietary fibers from brewer's grains, the onedescribed in Japanese Post-Unexamined Patent Publication (Kokoku) No.4-31666 can be used. Thus, the brewer's grains in the wet state aretreated by pressing and milling and the pressed and milled product thusobtained may be sieved in the presence of water. The fraction that haspassed through the sieve is the substance containing proteins andinsoluble dietary fibers. More particularly, brewer's grains in the wetstate are first treated by pressing and milling. Although any pulverizercan be used that has a structure capable of exerting a compressive forceon the raw material to be treated for pressing and milling of thebrewer's grains, a roll mill is specifically preferred. The gap betweenthe rolls is 0.05 to 2 mm, preferably 0.1 to 0.3 mm. When the brewer'sgrains are to be pressed and milled, a water content in the brewer'sgrains is preferably adjusted to 65% or higher. Then the pressed andmilled product is sieved in the presence of water. In this sieving, thehusk remains on the sieve and the substance containing proteins andinsoluble dietary fibers passes through it. The size of the openings inthe sieve is 5 to 50 mesh, preferably 20 to 50 mesh. In order to obtainefficiently the fraction containing proteins and insoluble dietaryfibers, the above-mentioned pressing and milling and sieving operationsare preferably repeated 2 to 5 times. The fractions thus obtained as theundersizes through the sieve are usually dried before use. The dryingmethods include, but are not limited to, drying with warm air at atemperature of 50 to 100° C., and lyophilization. In some cases, thefractions may be used in the wet state, where their water content ispreferably adjusted to about 10 to 90%.

The dispersibility of the material into water may be enhanced byconverting the contained proteins into smaller molecules using anenzyme, etc. For example, the substance containing proteins andinsoluble dietary fibers is dispersed in water of pH 9, which is thensubjected to a thermal dispersing treatment such as autoclaving. Afterthe temperature of the dispersion has risen to 50° C., alkali protease(such as Alkalase by Novo) is added to about 0.02% followed byincubation for about 24 hours, where upon the proteins are converted tosmaller molecules with an average peptide chain length of about 5 to 8.The average peptide chain length can be determined by the TNBS method(Nakamura et al., Nippon Shokuhin Kogyo Gakkaishi 38: 377-383, 1991).

Furthermore, the content of the insoluble dietary fibers may be enhancedby removing some of the protein fraction. In one method, for example,the substance containing proteins and insoluble dietary fibers istreated by artificial digestion (Matoba et al., Journal of JapaneseSociety of Food and Nutrition, 34: 415-421, 1981). In the method, thefraction of proteins and insoluble dietary fibers is sequentiallyreacted in a pepsin-hydrochloric acid solution and then in apancreatin-hydrochloric acid solution in order to yield an undigestedfraction. By this treatment, the content of dietary fibers can beenhanced to as high as 70% by weight. However, this is not the soleexamples of the methods that can be applied.

Oral administration of the substance containing proteins and insolubledietary fibers can not only alleviate severe diarrhea derived fromulcerative colitis, but daily intake of the substance can increaseresistance to ulcerative colitis itself. For this purpose, the substancecontaining proteins and insoluble dietary fibers is preferally taken inat least 1 g, more preferably at least 12 g, per day. Since thesubstance containing proteins and insoluble dietary fibers is derivedfrom the germinated seed of a grass family plant, it will do no harmeven if it is taken excessively and, hence, it can be adopted in dailyeating programs. The administration or intake of the substance may betimed before, between, or after meals.

The substance containing proteins and insoluble dietary fibers may beused to prevent or reduce the side effects of cancer treatments. Themethods of cancer treatment include the radiation therapy in which aradiation such as gamma rays are applied, the chemotherapy in whichanti-cancer drugs such as methotrexate and fluorouracil areadministered, and combinations of these methods.

The side effects of cancer treatments include damages to intestinalmucosa and the resultant diarrhea. In accordance with the presentinvention, the substance containing proteins and insoluble dietaryfibers may be given at least one day, preferably one week, before cancertreatment. Alternatively, the substance containing proteins andinsoluble dietary fibers may be given concomitantly with or after cancertreatment. The daily dosage for adults is 1 g or more, preferably 12 gor more. The substance is derived from the germinated seed of a grassfamily plant, so it will do no harm even if it is taken excessively.Accordingly, it is preferably administered continuously during thecancer treatment.

Oral intake of the substance containing proteins and insoluble dietaryfibers can promote improvement in the bowel movement of a patient whohas undergone massive ablation of the bowels or a patient who wears anartificial anus. For this purpose, the proteins and insoluble dietaryfibers are preferably taken in at least 4 g, more preferably at least 12g, per day, Since the proteins and insoluble dietary fibers arecomponents derived from the germinated seed of a grass family plant, itwill do no harm even if it is taken excessively.

The substance containing proteins and insoluble dietary fibers accordingto the present invention may be added to foods and beverages. Examplesof the foods and beverages to which the substance containing proteinsand insoluble dietary fibers according to the present invention can beadded include those containing natural products or processed products asthe derivatives. The substance can be added in an amount of 0.01 to 1 gper gram of food or beverage. The substance containing proteins andinsoluble dietary fibers according to the present invention can be addedto foods and beverages in various dosage forms such as solutions,suspensions, powders, granules, capsules, and the like.

The substance containing proteins and insoluble dietary fibers accordingto the present invention which can be formulated as a pharmaceuticalpreparation. In this case, the mode of drug administration is in no waybut exemplary routes of administration may be peroral, enteral and thelike. In the case of oral or enteral administration, the substancecontaining proteins and insoluble dietary fibers can be administered asit is or alternatively it can be administered in the form of a solution,a suspension, powder, granule, a tablet, a capsule, and the like incombination with a pharmaceutically acceptable excipient. In this case,the preparation contains the above substance containing proteins andinsoluble dietary fibers according to the present invention in asuitable amount of 1 to 50%, preferably 1 to 30%. Examples of theexcipient include: sugars such as lactose,sucrose and glucose; starch,inorganic substances such as calcium carbonate and calcium sulfate; andother commonly used substances such as crystalline cellulose, distilledwater, purified water, sesame oil, soybean oil, corn oil, olive oil, andcotton seed oil. In formulating pharmaceutical preparations, additivessuch as binders, lubricants, dispersants, suspending agents,emulsifiers, diluents, buffers, anti-oxidants, anti-bacterial agents canbe used. Other pharmaceutical preparations may be mixed or used incombination. The above preparations may be sterilized.

The present invention is now explained in further detail with referenceto the following examples. It should be noted, however, that the scopeof the present invention is not limited by these examples in any way.Unless otherwise specified, % means present by weight in the examples.

FORMULATION EXAMPLE 1

Brewer's grains in the wet state (water content: 77.6% by weight) werepressed and milled (the rotating speed of the roller: 100 rpm, the gapbetween rolls: 0.1 mm), and then screened using a 50 mesh sieve. Thefraction that passed through the sieve was dried using a steam dryer andthen crushed to give a substance containing proteins and insolubledietary fibers. The analytical values of the substance were as shown inTable 1 and 2.

Crude protein as shown in Table 1 was determined using Kjeldahl method(the coefficient of nitrogen conversion to protein was set at 6.25),crude fat was determined using the soxhlet extraction method withdiethyl ether as the extraction solvent, the ash content was determinedby the direct in cineration method with the sample placed in a crucible,and the dietary fiber content was determined by calculating the sum ofthe amounts of hemicellulose, cellulose, and lignin shown in Table 2.

The analyses of hemicellulose, cellulose, and lignin shown in Table 2were carried out based on the method described in “Dietary Fiber,”Innami and Kiriyama eds., pp. 38-40, 1989, Daiichi Shuppan.

TABLE 1 Table of Ingredients (% by weight) Crude protein 53.4 Crude fat12.6 Ash content  2.0 Dietary fiber 32.1

TABLE 2 Composition of Dietary fiber (%) Hemicellulose 50.0 Cellulose24.0 Lignin 26.0

FORMULATION EXAMPLE 2

With the gap between rolls adjusted to 2 mm, a different kind ofbrewer's grains was treated as in Formulation Example 1 to give thesubstance containing proteins and insoluble dietary fibers which wasderived from the brewer's grains and which contained different amountsof proteins and insoluble dietary fibers. The analytical values of thesubstance are shown in Table 3.

TABLE 3 Composition of the substance containing proteins and insolubledietary fibers as obtained in Formulation Example 3 Ingredients (% byweight) Crude protein 56.1 Crude fat 12.0 Ash content  2.8 Dietary fiber28.9

FORMULATION EXAMPLES 3 AND 4

Using the same method as shown in Formulation Example 2 except that adifferent kind of brewer's grains was used as the raw material and thatthe conditions of the roll mill and screening in water were modified,the substance containing proteins and insoluble dietary fibers wasobtained which was derived from the brewer's grains and which containeddifferent amounts of proteins and insoluble dietary fibers. Theanalytical values of the substance are shown in Table 4.

TABLE 4 Composition of proteins and insoluble dietary fibers ofFormulation Examples 3 and 4 (% by weight) Formulation FormulationIngredients Example 3 Example 4 Crude protein 34.9 60.0 Crude fat 12.012.0 Ash content  3.0  2.8 Dietary fiber 50.1 25.0

FORMULATION EXAMPLE 5

Starting with the substance containing proteins and insoluble dietaryfibers which obtained in Formulation Example 1, a material having gooddispersibility in water was prepared.

Fifty grams (in the dry state) of the substance containing proteins andinsoluble dietary fibers as obtained in Formulation Example 1 wasweighed, adjusted to pH 9 with sodium hydroxide and further adjusted tomake 1 liter. The mixture was subjected to a heat treatment such asautoclaving (121° C., 10 min) and then cooled to 50° C. Thereafter,about 0.02% of alkaline protease (such as Alkalase by Novo) followed byincubation for 24 hours.

Subsequently, thermal-denaturing of the enzyme and lyophilization wereconducted. The lyophilized product was crushed to yield a substancehaving good dispersibility in water.

The average peptide chain length of the substance was determined by theTNBS method (Nakamura et al., Nippon Shokuhin Kogyo Gakkaishi 38:377-383, 1991) and found to be about 5 to 8.

FORMULATION EXAMPLE 6

A material with an enhanced content of dietary fibers was prepared fromthe substance containing proteins and insoluble dietary fibers that hadbeen obtained in Formulation Example 1.

One hundred grams of the fraction obtained in Formulation Example 1 wastaken as a sample; 1600 ml of an enzyme solution (0.087% pepcin/0.096 NHCl+0.03 M NaCl) and, furthermore, 1200 ml of 0.1 M NaHCO3 were added.The mixture was thermally denatured by incubating at 37° C. f or 4hours. washing with water was performed until a neutral filtrate cameout; thereafter, 1000 ml of an enzyme solution (2.17%pancreatin/Tris-HCl 0.5 M, pH8) and, furthermore, 4000 ml of 0.01 N HClwere added. The mixture was thermally denatured by incubating at 37° C.for 24 hours or longer (26 hours in this case); it was then washed,filtered, lyophilized and crushed. By these treatments, the proteincontent became 15% and the dietary fiber content 70%.

TEST EXAMPLE 1

The substance containing proteins and insoluble dietary fibers that wasprepared in Formulation example 1 was tested to determine whether itcould treat the severe diarrhea from ulcerative colitis or abnormalitiesin the mucosa of colon.

Materials and Methods

As the test animal, male SD rats (3-week old, about 50 g) that had beenacclimated to the experimental condition by a preparatory breeding withthe solid feed (CE-2, Nippon clea) for one week were used in groups offive animals each. The feeds used in Test Example 1 were as shown inTable 5.

Ulcerative colitis was experimentally developed by giving the animal thefeed mixed with dextran sodium sulfate. This is a modification ofIwanaga's method (Journal of Gastroenterology 29: 430-438, 1994). Thesubstance containing proteins and insoluble dietary fibers was alsogiven ad libitum in a mixture with the feed. After breeding for 5 days,the appearances of the stool and the anus were examined and the state ofdiarrhea was evaluated by scoring. Then the colon was excised and fixedin 10% formalin buffer to prepare sections of the mucosa, and themicroscopic view of the mucosa were also examined.

Table 5 Composition of the feed

The basic feed was prepared so as to contain 10% of protein from casein,5% of lipid from corn oil, 1% of vitamin, 3.5% of minerals, and 0.2% ofcholine chloride. The weight was adjusted using corn starch.

Comparative Group 1

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1. Then, dextran sodium sulfate was added at 4%to induce ulcerative colitis. Experiment Group 1: After the substancecontaining proteins and insoluble dietary fibers according toFormulation Example 1 was added to the basic feed at 10%, dextransulfate sodium was added at 4% to induce ulcerative colitis.

Comparative Experiment Group 1 Group 1 (% by weight) Casein 14.6 10Mineral mix*¹ 3.5 3.5 Vitamin mix*² 1 1 Starch 68.7 66.3 Corn oil 5 5Cellulose 3 The substance containing 10 proteins and insoluble dietaryfibers according to Formulation example 1 Dextran sodium sulfate 4 4Choline chloride 0.2 0.2 *¹in conformity with AIN-93 *²in conformitywith AIN-93

Results

The results are shown in FIG. 1 through 3. FIG. 1 shows the diarrheascores of Experiment Group 1 and Comparative Group 1. The diarrhea scoreof FIG. 1 is the average of scores assigned to the rats in each group onthe basis of the following 6-level rating: 0, normal; 1, slightly soft;2, considerably soft; 3, stools cannot be picked up; 4,diarrhea+slightly eroded anus; 5, diarrhea+badly eroded anus. FIG. 2shows the appearance of stools from Comparative Group 1 (2-1) andExperiment Group 1 (2-1) FIG. 3 shows the appearance of the colonmucosas of Experiment Group 1 and Comparative Group 1. As shown in FIG.1 through 3, amelioration in diarrhea and prevention of damages in thecolon mucosa were observed only when the substance containing proteinsand insoluble dietary fibers was taken in. Similarly, diffusion of anuswas also prevented only when the substance containing proteins andinsoluble dietary fibers was taken in. In both of FIG. 2 and FIG. 3,only one case is illustrated for each experiment group, but normalimages of the mucosa were observed in 4 out of 5 animals in the groupthat took the substance containing proteins and insoluble dietaryfibers. As can be seen from this example, the substance containingproteins and insoluble dietary fibers effectively promotes ameliorationof symptoms.

Similar results have been obtained for the substance containing proteinsand insoluble dietary fibers according to the Formulation Examples 2through 4.

TEST EXAMPLE 2

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 1 was tested to determine whether it could treatsevere diarrhea associated with ulcerative colitis or abnormalities inthe mucosa of colon.

Materials and Methods

These were basically the same as in Test Example 1, but ulcerativecolitis was developed by 5-day breeding of all rats with the feed ofComparative Group 1 (the control group) described in Test Example 1;then, the rats were bred for 3 days, with the feed containing no dextransodium sulfate as shown in Table 6 and the degree of recovery fromdiarrhea was evaluated by scoring in a similar manner to Test Example 1.From the results of Test Example 1, it was concluded that in the casesof complete recovery from diarrhea, the mucosa of the colon was veryclose to the normal state.

Table 6 Composition of the Feed

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 2

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1.

Experiment Group 2

The substance containing proteins and insoluble dietary fibers accordingFormulation Example 1 was added to the basic feed at 10%.

Experiment Group 3

Salazosulfapyridine (salazopyrine: manufactured by Green Cross K.K.) wasadded to the feed of Comparative Group 2 at 0.5 g/kg feed (so that theapproximate dose would be equal to 50 mg/kg body weight). The dose ofsalazosulfapyridine was decided by referring to Folia. Pharmacol. Jpn.102: 343-350 (1993).

Comparative Experiment Experiment Group 2 Group 2 Group 3 (% by weight)Casein 14.6 10 14.6 Mineral mix*¹ 3.5 3.5 3.5 Vitamin mix*² 1 1 1 Starch72.7 70.3 72.65 Corn oil 5 5 5 Cellulose 3 3 The substance containing 10proteins and insoluble dietary fibers according to Formulation Example 1Salazopyrine 0.05 Choline chloride 0.2 0.2 0.2 *¹in conformity withAIN-93 *²in conformity with AIN-93

Results

The results are shown in FIG. 4. FIG. 4 shows the diarrhea scores ofExperiment Groups 2 and 3, and Comparative Group 2. Evaluation byscoring was made in a similar manner to Test Example 1. As shown in FIG.4, recovery from diarrhea was very fast in the group that was given thesubstance containing proteins and insoluble dietary fibers. The degreewas significantly better than from salazosulfapyridine, a drug currentlyused as a therapeutic drug for ulcerative colitis. The presentexperiment has shown that the administration of the substance containingproteins and insoluble dietary fibers can effectively promoteamelioration of symptoms even if it is taken after development ofulcerative colitis. Similar results are confirmed for the substancecontaining proteins and insoluble dietary fibers according toFormulation Examples 2 through 4.

TEST EXAMPLE 3

The substance containing proteins and insoluble dietary. fibers preparedin Formulation Example 5 was tested to determine whether it could treatsevere diarrhea associated with ulcerative colitis or abnormalities inthe mucosa of colon.

Materials and Methods

These were basically the same as in Test Example 1. The feeds used inTest example 3 were as shown in Table 7. After breeding for 5 days, theappearances of the stool and the anus were examined and the appearanceof diarrhea was evaluated by scoring.

Table 7 Table of Feed Composition

The method of preparing the basic feed was the same as in Test Example1.

Test Example Group 3

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 5. Then, dextran sodium sulfate was added theretoat 4% to induce ulcerative colitis.

Experiment Group 4

The substance containing proteins and insoluble dietary fibers ofFormulation Example 5 was added to the basic feed at 10%, and dextransulfate sodium was added at 4% to induce ulcerative colitis.

Comparative Experiment Group 3 Group 4 (% by weight) Casein 14.6 10Mineral mix*¹ 3.5 3.5 Vitamin mix*² 1 1 Starch 68.7 66.3 Corn oil 5 5Cellulose 3 The substance containing 10 proteins and insoluble dietaryfibers according to Formulation example 5 Dextran sodium sulfate 4 4Choline chloride 0.2 0.2 *¹in conformity with AIN-93 *²in conformitywith AIN-93

Results

The results are shown in FIG. 5. FIG. 5 shows the diarrhea scores ofExperiment Group 4, and Comparative Group 3. Evaluation by scoring wasmade in a similar manner to Test example 1. As shown in FIG. 5, thesubstance containing proteins and insoluble dietary fibers ofFormulation Example 5 has also shown a very marked amelioration of mainsymptoms of ulcerative colitis.

TEST EXAMPLE 4

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 6 was tested to determine whether it could treatsevere diarrhea associated with ulcerative colitis or abnormalities inthe mucosa of colon.

Materials and Methods

As the test animal, male Std-ddY mice (6-week old, about 30 g) that hadbeen acclimated to the experimental condition by a preparatory breedingwith the solid feed (CE-2, Nippon clea) for one week were used in groupsof five animals each. The feeds used in Test Example 4 were as shown inTable 8.

Ulcerative colitis was experimentally developed by giving the animal thefeed mixed with dextran sodium sulfate. This is a modification ofIwanaga's method (Journal of Gastroenterology 29: 430-438, 1994). Thesubstance containing proteins and insoluble dietary fibers was alsogiven ad libitum in a mixture with the feed. After breeding for 3 days,the appearances of the stool and the anus were examined on day 4 and thestate of diarrhea was evaluated by scoring.

Table 8 Composition of the Feed

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 4

Dextran sodium sulfate was added to the basic feed at 4% to induceulcerative colitis.

Experiment Group 5

After the substance containing proteins and insoluble dietary fibersaccording to Formulation Example 6 was added to the basic feed at 5%,dextran sodium sulfate was added at 4% to induce ulcerative colitis.

Comparative Experiment Group 1 Group 1 (% by weight) Casein 10 10Mineral mix*¹ 3.5 3.5 Vitamin mix*² 1 1 Starch 73.3 71.3 Corn oil 5 5Cellulose 3 The substance containing 5 proteins and insoluble dietaryfibers according to Formulation Example 6 Dextran sodium sulfate 4 4Choline chloride 0.2 0.2 *¹in conformity with AIN-93 *²in conformitywith AIN-93

Results

The results are shown in FIG. 6. FIG. 6 shows the diarrhea scores ofExperiment Group 5 and Comparative Group 4. Evaluation by scoring wasmade in a similar manner to Test Example 1. As shown in FIG. 6, thesubstance containing proteins and insoluble dietary fibers according toFormulation Example 6 has also shown a very effective amelioration ofmain symptoms of ulcerative colitis.

TEST EXAMPLE 5

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 1 was tested to determine whether it couldprevent or ameliorate severe damages on the mucosa of colon and diarrheawhen anti-cancer agents were being used.

Materials and Methods

Male SD rats (4-week old), after preparatory breeding with the solidfeed (CE-2, Nippon clea) for one week, were divided into groups of fiveanimals each (body weight at the time of grouping was 136.2 g). Theywere then bred for one week by giving ad libitum the feed shown in Table9. On day 7, 8 and 9, methotrexate (manufactured by Nippon Lederle) wasgiven intraperitoneally at 5 mg/kg body weight. The animals were furtherbred for 5 days, and on day 5, after fasting for 4 hours, the jejunum(portions at 15 to 30 cm from the pylorus) was taken out underanesthesia with urethane. It was then fixed in formalin and embeddedwith paraffin and stained with hematoxylin-eosin for microscopicobservation.

The following comparative examples were set up: 1) a comparative controlgroup (cellulose was used as a dietary fiber) and 2) a group to whichglutamin commonly held as an ideal nutrient for intestinal mucosa wasadded. On the last three days, stools were collected and their dryweight was measured.

Table 9 Table of Feed Composition

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 1a

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1.

Experiment Group 1a

The substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1 was added to the basic feed at 10%.

Experiment Group 2a

Glutamin was added to the basic feed at 1.13%. This is equivalent to thecontent of glutamin obtained when the substance containing proteins andinsoluble dietary fibers was added to the feed at 10%. Furthermore,casein and cellulose were added so that the weights of proteins anddietary fibers would be the same as in Experiment Group 1a.

Comparative Experiment Experiment Group 1a Group 1a Group 2a (% byweight) Casein 14.6 10 13.47 Mineral mix*¹ 3.5 3.5 3.5 Vitamin mix*² 1 11 Starch 72.7 70.3 72.7 Corn oil 5 5 5 Cellulose 3 3 The substancecontaining 10 proteins and insoluble dietary fibers according toFormulation Example 1 Glutamin 1.13 Choline chloride 0.2 0.2 0.2 *¹inconformity with AIN-93 *²in conformity with AIN-93

Results

The results are shown in FIGS. 8 and 9. FIG. 8 shows the dry weight ofthe stools from Experiment Group 1a and Comparative Group 1a and 2a.Comparative Groups 1a and 2a had severe diarrhea. FIG. 9 shows theappearance of the mucosas of the small intestines of Experiment Group 1aand Comparative Groups 1a and 2a (9-2, 9-1, and 9-3, respectively) Asshown in FIGS. 8 and 9, excretion of the stool was normal in ExperimentGroup 1a that took the substance containing proteins and insolubledietary fibers, but a reduction in the dry weight of stool excretion wasobserved in Comparative Groups 1a and 2a due to diarrhea. In theexamination of the mucosa of the intestine, images of normal mucosa wereobserved only when the substance containing proteins and insolubledietary fibers was taken and this suggests that the substance protectsthe intestinal mucosa from side effects of the anti-cancer agent.

TEST EXAMPLE 6

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 1 was tested to determine whether it could reduceor prevent the damage that would otherwise be caused on the intestinalmucosa by radiation exposure.

Materials and Methods

Male ST-Wistar rats (3-week old), after preparatory breeding with thecasein-sucrose diet (the basic feed or Comparative Group 3a as shown inTable 10) for one week, were divided into groups of seven animals each.Subsequently, the animals were fed the test feed shown in Table 10 for10 days, and on day 11 they were exposed to a radiation of 10 Gy (from60Co) in a localized area (lower abdomen). They were bred for 8 moredays and the effect of the substance containing proteins and insolubledietary fibers to prevent the damage on the intestinal mucosa due toradiation exposure was evaluated in terms of the survival rate.

Table 10 Table of Feed Composition

Comparative Group 3a

The sucrose basic feed group with 20% casein and 0% dietary fiber

Experiment Group 2a

The substance containing proteins and insoluble dietary fibers preparedin Formulation example 1 was added to the sucrose basic feed at 10% andits sucrose content was accordingly reduced.

Comparative Experiment Group 3a Group 2a (% by weight) Casein 20 20Mineral mix 3.5 3.5 Vitamin mix 1 1 Starch 70.3 60.3 Corn oil 5 5 Thesubstance containing 10 proteins and insoluble dietary fibers accordingto Formulation example 1 Choline chloride 0.2 0.2

Results

As shown in Table 11, a reduction in mortality was observed only whenthe substance containing proteins and insoluble dietary fibers was takenby the test animals. This is believed to result from the reduction inthe radiation damage on the intestinal mucosa.

TABLE 11 Survival rate on day 8 of radiation exposure ComparativeExperiment Group 3a Group 2a (No. of viable animals/total No. tested)(5/7) (7/7)

TEST EXAMPLE 7

The substance containing proteins and insoluble dietary fibers preparedin Formulation example 1 was tested to determine whether it would permitnormal stool formation when a massive ablation of the lowergastrointestinal tract (the large intestine) was carried out.

Materials and Methods

As the test animal, male SD rats (4-week old, about 50 g) that had beenacclimated to the experimental condition by a preparatory breeding withthe feed shown in Table 12 for one week were used in groups of 10animals each. The large intestine was removed in such a way that theanus and the large intestine within the pelvis were left intact; then,an end-to-end anastomosis of the small intestine was conducted. After arecovery period of 2 days, the animals were given again the feed shownin Table 12 and bred for one week, and the appearance of the stool andthe anus were examined.

Table 12 Table of Feed Composition

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 1b

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1.

Experiment Group 1b

The substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1 was added to the basic feed at 10%.

Comparative Experiment Group 1b Group 1b (% by weight) Casein 14.6 10Mineral mix*¹ 3.5 3.5 Vitamin mix*² 1 1 Starch 72.7 70.3 Corn oil 5 5Cellulose 3 The substance containing 10 proteins and insoluble dietaryfibers according to Formulation Example 1 Choline chloride 0.2 0.2 *¹inconformity with AIN-93 *²in conformity with AIN-93

Results

Examination of the stool and the anus was conducted on the last day ofbreeding and the results are shown in FIGS. 10 and 11: fairly severediarrhea with liquid stools was noted in Comparative Group 1b whereasthe stool had an almost normal appearance in Experiment Group 1b.

Examination of the periphery of the anus revealed that severe erosiondue to diarrhea was noted in Comparative Group 1b whereas no erosion wasobserved to give an almost normal appearance in Experiment Group 1bbecause of the component of interest in Formulation Example 1.

The substance containing proteins and insoluble dietary fibers permittednormal stool formation very effectively after ablation of thegastrointestinal tract.

FORMULATION EXAMPLE 7

After accurate weight measurement, dry barley malt was scraped from thehusk surface with TDB2A, a rice whiting machine for brewery use(manufactured by Satake Seisakusho; working rotational speed, 500 rpm).The scraped malt grains which weighed 88-80% of the initial barley maltwere obtained as the substance containing proteins and insoluble dietaryfibers. Its protein and dietary fiber contents were 11.5% and 30%,respectively.

For comparison, ungerminated barley was fractionated under the sameconditions as described above. The resulting substance containingproteins and insoluble dietary fibers had protein and dietary fibercontents of 16.3% and 31.5%, respectively.

FORMULATION EXAMPLE 8

Germinated rice was dried and dehusked. After accurate weightmeasurement, the dehusked grains were scraped from the surface withTDB2A, a rice whiting machine for brewery use (manufactured by SatakeSeisakusho; working rotational speed, 500 rpm). The scraped rice grainswhich weighed 100-95% of the initial rice grains were obtained as thesubstance containing proteins and insoluble dietary fibers. Its proteinand dietary fiber contents were 17.6% and 21.6%, respectively.

For comparison, ungerminated brown (dehusked) rice was fractionatedunder the same conditions as described above. The resulting substancecontaining proteins and insoluble dietary fibers had protein and dietaryfiber contents of 16.3% and 28.5%, respectively.

TEST EXAMPLE 8

The effect of the substance containing proteins and insoluble dietaryfibers prepared in Test Examples 7 and 8 was investigated.

Materials and Methods

The same as in Test Example 1. The feeds used in Test Example 8 were asshown in Table 13.

Table 13 Table of Feed Composition

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 5

Same as the feed for Experiment Group 6, except that no substancecontaining proteins and insoluble dietary fibers was added and that itwas supplemented with casein and cellulose to provide the correspondingprotein and dietary fiber contents. It contained 3.5% of dextran sodiumsulfate in order to induce ulcerative colitis.

Comparative Group 6

The substance containing proteins and insoluble dietary fibers which wasderived from “ungerminated barley” and prepared in Formulation Example 7was added to the basic feed at 10%, and dextran sodium sulfate was addedat 3.5% in order to induce ulcerative colitis.

Experiment Group 6

The substance containing proteins and insoluble dietary fibers which wasderived from barley malt and prepared in Formulation Example 7 was addedto the basic feed at 10%, and dextran sodium sulfate was added at 3.5%in order to induce ulcerative colitis.

Comparative Group 7

The substance containing proteins and insoluble dietary fibers which wasderived from “ungerminated brown rice” and prepared in FormulationExample 8 was added to the basic feed at 10%, and dextran sodium sulfatewas added at 3.5% in order to induce ulcerative colitis.

Experiment Group 7

The substance containing proteins and insoluble dietary fibers which wasderived from germinated rice grains and prepared in Formulation Example8 was added to the basic feed at 10%, and dextran sodium sulfate wasadded at 3.5% in order to induce ulcerative colitis.

Comp. Comp. Exp. Comp. Exp. Group 5 Group 6 Group 6 Group 7 Group 7 (%by weight) Casein 14.6 13.0 13.3 13.0 12.8 Mineral mix 1 1 1 1 1 Vitaminmix 3.5 3.5 3.5 3.5 3.5 Starch 69.4 64.0 63.55 63.85 63.36 Cellulose 30.15 0.15 0.84 Corn oil 5 5 5 5 5 The substance containing proteins 10and insoluble dietary fibers derived from ungerminated barley accordingto Formulation Example 7 The substance containing proteins 10 andinsoluble dietary fibers derived frorn barley according to FormulationExample 7 The substance containing proteins and insoluble dietary fibersderived from ungerminated brown rice according to Formulation Example 810 The substance containing proteins 10 and insoluble dietary fibersderived from germinated rice according to Formulation Example 8 Dextransodium sulfate 3.5 3.5 3.5 3.5 3.5

Results

The results of the investigation on Experiment Groups 6 and 7, andComparative Groups 5 through 7 described in Table 13 are shown in FIG.7. The diarrhea scores in FIG. 7 were evaluated in the same manner as inTest Example 1.

As shown in FIG. 7, the diarrhea score decreased only when thesubstances containing proteins and insoluble dietary fibers that derivedfrom the germinated barley and the germinated rice was taken by theanimals. Therefore, it was demonstrated that both of these substancescontaining proteins and insoluble dietary fibers can prevent the severediarrhea associated with ulcerative colitis.

In Test Example 8, none of the experiment groups showed measurablechanges in body weight.

FORMULATION EXAMPLE 9

After accurate weight measurement, dried and dehusked rye malt wasscraped from the grain surface with TDB2A, a rice whiting machine forbrewery (manufactured by Satake Seisakusho; working rotational speed,500 rpm).

The scraped rye malt grains which weighed 100-96% of the initial ryemalt grains were obtained as the substance containing proteins andinsoluble dietary fibers. Its protein and dietary fiber contents were16.3% and 35%, respectively.

FORMULATION EXAMPLE 10

After accurate weigh measurement, dried and dehusked rye was scrapedfrom the grain surface with TDB2A, a rice whiting machine for breweryuse (manufactured by Satake Seisakusho; working rotational speed, 500rpm). The scraped rye grains which weighed 100-96% of the initial ryegrains were obtained as the substance containing proteins and insolubledietary fibers. Its protein and dietary fiber contents were 12.9% and35%, respectively.

The analytical values of these substances are as shown in Table 14.

TABLE 14 Table of ingredients Formulation Example 9 Formulation Example10 (% by weight) Crude protein 16.3 12.9 Crude fat 3.8 4.2 Ash content2.6 3.7 Dietary fiber 35.0 35.0

TEST EXAMPLE 9

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 9 was tested to determine whether it could treatthe severe diarrhea associated with ulcerative colitis or abnormalitiesin the mucosa of colon. The same test was conducted with the fractionsobtained in Formulation Example 10.

Materials and Methods

As the test animal, male SD rats (3-week old, about 50 g) that had beenacclimated to the experimental condition by a preparatory breeding witha solid feed for one week were used in groups of five animals each. Thefeeds used in Test Example 9 were as shown in Table 15.

The substances containing proteins and insoluble dietary fibers preparedin Formulation Examples 9 and 10 were also given ad libitum in admixturewith the feed. After breeding for 5 days, the appearance of the stooland the anus was examined and the severity of diarrhea was evaluated byscoring. Then the colon was ablated totally and fixed in 10% formalin toprepare sections of the mucosa, and the images of the mucosa were alsoexamined. The results were, as shown in Table 16; the amelioration ofdiarrhea and the prevention of erosion in the anus and damage on themucosa of the large intestine were possible only when the substancecontaining proteins and insoluble dietary fibers prepared in FormulationExample 9 was taken by the animals.

The severity of diarrhea was classified into 6 levels: 0, normal; 1,slightly soft; 2, considerably soft; 3, stools could not be picked up;4, diarrhea+slightly eroded anus; 5, diarrhea+badly eroded anus. Also,the damage on the mucosa of the large intestine was scored in accordancewith the method of Morris, in which the larger number means a severerdamage.

Table 15 Table of Feed Composition

The method of preparing the basic feed was the same as in Test Example1.

Comparative Group 1c

The basic feed was supplemented with casein and cellulose to provide theprotein and dietary fiber contents that would be given by adding 10% ofthe substance containing proteins and insoluble dietary fibers accordingto Formulation Example 1. Dextran sodium sulfate was added at 4% toinduce ulcerative colitis.

Comparative Group 2c

The substance containing proteins and insoluble dietary fibers accordingto Formulation Example 10 was added to the basic feed at 10%, anddextran sodium sulfate was added at 4% in order to induce ulcerativecolitis. Casein and cellulose were also added to give the same proteinand dietary fiber contents as in Comparative Group 1c.

Experiment Group 1c:

The substance containing proteins and insoluble dietary fibers accordingto Formulation Example 9 was added to the basic feed at 10%, and dextransodium sulfate was added at 4% in order to induce ulcerative colitis.Casein and cellulose were also added to give the same protein anddietary fiber contents as in Comparative Group 1c.

Comparative Experiment Experiment Group 1c Group 2c Group 1c (% byweight) Casein 14.6 13.3 12.9 Mineral mix*¹ 3.5 3.5 3.5 Vitamin mix*² 11.0 1.0 Starch 68.7 63.0 63.4 Corn oil 5.0 5.0 5.0 Cellulose 3.0 Thesubstance containing 10.0 proteins and insoluble dietary fibersaccording to Formulation Example 10 The substance containing 10.0proteins and insoluble dietary fibers according to Formulation Example 9Dextran sodium sulfate 4.0 4.0 4.0 Choline chloride 0.2 0.2 0.2 *¹inconformity with AIN-93 *²in conformity with AIN-93

Results

The results of the above experiment were as shown in Table 16. Thesubstance containing proteins and insoluble dietary fibers prepared inTest Example 9 was capable of treating the diarrhea peculiar toulcerative colitis and it was also very effective in preventing thedamage that would otherwise be caused on the mucosa of the largeintestine.

TABLE 16 Score of damage on the mucosa Diarrhea score of the largeintestine Comparative Group 1c 5.0 4.2 Comparative Group 2c 3.8 5.7Experiment Group 1c 0.4 2.5

FORMULATION EXAMPLE 11

The method shown in Formulation Example 2 was repeated, except that adifferent kind of brewer's grains was used as the raw material and thatthe drying with dry heat (steam dryer) was replaced by lyophilization.Thus, the brewer's grains in the wet state were pressed and milled andthen screened using a 50-mesh sieve within water. The fraction thatpassed through the sieve was subjected to preliminary freezing at −20°C. and then lyophilized according to the standard method.

The results of analysis are shown in Tables 17 and 18.

TABLE 17 Table of Ingredients (% by weight) Crude protein 50.2 Crude fat13.7 Ash content 1.5 Dietary fiber 33.6

TABLE 18 Composition of Dietary fibers (%) Hemicellulose 69.9 Cellulose23.3 Lignin 6.8

A test was conducted with the substance as shown below.

TEST EXAMPLE 10

The substance containing proteins and insoluble dietary fibers preparedin Formulation Example 11 was tested to determine whether it could treatthe severe diarrhea associated with ulcerative colitis or abnormalitiesin the mucosa of the large intestine.

Materials and Methods

The test animals and the method of developing ulcerative colitis were asshown in Test Example 1, except that the feeds used in Test Example 10were as shown in Table 19 below.

TABLE 19 Comparative Experiment Example 1 Example 1 (% by weight) Casein14.6 10 Mineral mix*¹ 3.5 3.5 Vitamin mix*² 1.0 1.0 Starch 69.2 66.8Corn oil 5.0 Cellulose 3.0 The substance containing proteins 10.0 andinsoluble dietary fibers according to Formulation Example 11 Cholinechloride 0.2 0.2 dextran sodium sulfate 3.5 3.5 *¹in conformity withAIN-93 *²in conformity with AIN-93

Results

The results are shown in Table 20. In Experiment Example 1 the diarrheascore decreased and no erosion was observed in the periphery of theanus.

TABLE 20 Comparative Example 1 5.0 Experiment Example 1 0.2

It will be readily recognized by a person skilled in the art that asidefrom the substances tested in the above Test Examples, those which arederived from the germinated seeds of plants of a grass family which arewithin the scope of the present invention would have similar effects.

INDUSTRIAL APPLICABILITY

The substance derived from the germinated seed of a grass family plantof the present invention is capable of treating the diarrhea associatedwith ulcerative colitis and it is also effective in preventing disordersof the mucosa of the large intestine. In addition, the substance derivedfrom the germinated seed of a grass family plant of the presentinvention can effectively prevent damages on the intestinal mucosa andcontrol the ensuing onset of diarrhea, both symptoms being severe sideeffects resulting from administration of anti-cancer agents.Furthermore, the substance derived from the germinated seed of a grassfamily plant of the present invention can effectively improve the bowelmovement of a patient who has undergone intestinal ablation or a patientwith an artificial anus. Moreover, the substance derived from thegerminated seed of a grass family plant of the present invention has noside effects.

What is claimed is:
 1. A method of avoiding or reducing damage to theintestinal mucosa and the resultant diarrhea, the method comprisingadministering to a patient with a cancer an effective amount of asubstance which was isolated from the germinated seed of a barley, rice,or rye plant and which contains 10% to 70% protein by weight and 20 to70% insoluble dietary fiber by weight.
 2. A method of prophylactic ortherapeutic treatment of damage to the intestinal mucosa and theresultant diarrhea, comprising administering at least one gram of asubstance isolated from fractions containing the aleurone layer and thegerm of the germinated seed of a brewer's grain, said substancecomprising 10% to 70% protein by weight and 20 to 70% insoluble dietaryfiber by weight.
 3. A substance isolated from the germinated seed of abarley, rice, or rye plant which comprises 10 to 70% protein by weightand 20 to 70% insoluble dietary fiber by weight and wherein the isolatedsubstance is obtained by passing through a sieve of 50 mesh.
 4. Thesubstance of claim 3, wherein the substance comprises the aleurone layerand the germ of the germinated seed.
 5. A substance isolated from thegerminated seed of a barley, rice, or rye plant which comprises 10 to70% protein by weight and 20 to 70% insoluble dietary fiber by weight,wherein the isolated substance is obtained by passing through a sieve of50 mesh and the protein has been converted by enzyme treatment tosmaller molecules having an average length of about 5 to 8 amino acids.6. The substance of claim 5, wherein the substance comprises thealeurone layer and the germ of the germinated seed.
 7. A substanceisolated from the germinated seed of a barley, rice, or rye plant whichcomprises 10 to 70% protein by weight and 20 to 70% insoluble dietaryfiber by weight, wherein the isolated substance is obtained by passingthrough a sieve of 50 mesh and the concentration of insoluble dietaryfibers, relative to the concentration of protein, has been increased byenzyme treatment and filtration.
 8. The substance of claim 7, whereinthe substance comprises the aleurone layer and the germ of thegerminated seed.
 9. A method for preventing or reducing damage to theintestinal mucosa comprising administering to a patient in need thereofan effective amount of a substance isolated from the germinated seed ofa barley, rice, or rye plant, wherein the substance comprises 10 to 70%protein by weight and 20 to 70% insoluble dietary fiber by weight. 10.The method of claim 9, wherein the substance comprises the aleuronelayer and the germ of the germinated seed.
 11. The method of claim 9,wherein the proteins have been converted by enzyme treatment to smallermolecules having an average length of about 5 to 8 amino acids.
 12. Themethod of claim 9, wherein the concentration of insoluble dietaryfibers, relative to the concentration of protein, has been increased byenzyme treatment and filtration.
 13. The method of claim 9, wherein thedamage to the intestinal mucosa causes diarrhea.
 14. The method of claim9, wherein the damage to the intestinal mucosa is caused by a cancertreatment.
 15. A method for treating diarrhea, wherein the diarrhea iscaused by damage to the intestinal mucosa, comprising administering to apatient in need thereof an effective amount of a substance isolated fromthe germinated seed of a barley, rice, or rye plant, wherein thesubstance comprises 10 to 70% protein by weight and 20 to 70% insolubledietary fiber by weight.
 16. The method of claim 15, wherein thesubstance comprises the aleurone layer and the germ of the germinatedseed.
 17. The method of claim 15, wherein the proteins have beenconverted by enzyme treatment to smaller molecules having an averagelength of about 5 to 8 amino acids.
 18. The method of claim 15, whereinthe concentration of insoluble dietary fibers, relative to theconcentration of protein, has been increased by enzyme treatment andfiltration.
 19. The method of claim 15, wherein the damage to theintestinal mucosa is caused by a cancer treatment.